Person: Méndez López, Iván
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Méndez López
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Iván
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Ciencias de la Salud
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0000-0001-9792-6499
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124570
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Publication Open Access Hepatitis tóxica colestástica por clopidogrel en un paciente pluripatológico(Gobierno de Navarra. Departamento de Salud, 2016) Etxeberria Lekuona, Daniel; Méndez López, Iván; Mercado Gutiérrez, María R.; Oteiza Olaso, Julio; Arteaga Mazuelas, Miren; Jarne Betrán, Vanesa; Ciencias de la Salud; Osasun ZientziakEl clopidogrel es un fármaco antiagregante de la familia de la tienopiridinas muy utilizado en pacientes con cardiopatía isquémica, ictus y arteriopatía periférica. La toxicidad hepática por este fármaco es muy infrecuente. En la bibliografía únicamente se han descrito 16 casos, y solo en dos de ellos se practicó una biopsia hepática. Se presenta el caso de un paciente de 78 años pluripatológico que presentó una hepatitis tóxica colestásica severa por este fármaco y los hallazgos de la biopsia hepática que se le realizó. El cuadro se resolvió tras la retirada del fármaco. En base a los hallazgos de nuestro caso y los de los casos previamente publicados se revisan las características de la hepatitis tóxica por clopidogrel y su manejo diagnóstico y terapéutico.Publication Open Access Objetivos de presión arterial para la hipertensión en pacientes con enfermedad renal crónica(2022) Méndez López, Iván; Erviti López, Juan; Saiz Fernández, Luis Carlos; Ciencias de la Salud; Osasun ZientziakThe objective of this doctoral thesis is to determine whether intensive blood pressure targets are associated with a reduction in mortality and morbidity as compared with standard blood pressure targets in the treatment of people with hypertension and a history of CKD, defined as albuminuria, as a marker of kidney damage or decreased GFR. Kidney abnormalities defined in the studies as CKD are also considered as inclusion criteria.Publication Open Access Association of blood-based DNA methylation markers with late-onset alzheimer disease: a potential diagnostic approach(Lippincott Williams & Wilkins, 2023) Acha Santamaría, Blanca; Corroza, Jon; Sánchez Ruiz de Gordoa, Javier; Cabello, Carolina; Robles Solano, Maitane; Méndez López, Iván; Macías, Mónica; Zueco, Sara; Roldán, Miren; Urdánoz Casado, Amaya; Jericó Pascual, Ivonne; Erro Aguirre, María Elena; Alcolea, Daniel; Lleo, Alberto; Blanco Luquin, Idoia; Mendióroz Iriarte, Maite; Ciencias de la Salud; Osasun ZientziakBackground and Objectives: There is an urgent need to identify novel noninvasive biomarkers for Alzheimer disease (AD) diagnosis. Recent advances in blood-based measurements of phosphorylated tau (pTau) species are promising but still insufficient to address clinical needs. Epigenetics has been shown to be helpful to better understand AD pathogenesis. Epigenetic biomarkers have been successfully implemented in other medical disciplines, such as oncology. The objective of this study was to explore the diagnostic accuracy of a blood-based DNA methylation marker panel as a noninvasive tool to identify patients with late-onset Alzheimer compared with age-matched controls. Methods: A case-control study was performed. Blood DNA methylation levels at 46 cytosine-guanine sites (21 genes selected after a comprehensive literature search) were measured by bisulfite pyrosequencing in patients with “probable AD dementia” following National Institute on Aging and the Alzheimer's Association guidelines (2011) and age-matched and sex-matched controls recruited at Neurology Department-University Hospital of Navarre, Spain, selected by convenience sampling. Plasma pTau181 levels were determined by Simoa technology. Multivariable logistic regression analysis was performed to explore the optimal model to discriminate patients with AD from controls. Furthermore, we performed a stratified analysis by sex. Results: The final study cohort consisted of 80 patients with AD (age: median [interquartile range] 79 [11] years; 58.8% female) and 100 cognitively healthy controls (age 77 [10] years; 58% female). A panel including DNA methylation levels at NXN, ABCA7, and HOXA3 genes and plasma pTau181 significantly improved (area under the receiver operating characteristic curve 0.93, 95% CI 0.89–0.97) the diagnostic performance of a single pTau181-based model, adjusted for age, sex, and APOE ɛ4 genotype. The sensitivity and specificity of this panel were 83.30% and 90.00%, respectively. After sex-stratified analysis, HOXA3 DNA methylation levels showed consistent association with AD. Discussion: These results highlight the potential translational value of blood-based DNA methylation biomarkers for noninvasive diagnosis of AD. Registration Information: Research Ethics Committee of the University Hospital of Navarre (PI17/02218).Publication Open Access Early epigenetic changes of Alzheimer's disease in the human hippocampus(2020) Blanco Luquin, Idoia; Acha Santamaría, Blanca; Urdánoz Casado, Amaya; Sánchez Ruiz de Gordoa, Javier; Vicuña-Urriza, Janire; Roldán, Miren; Labarga Gutiérrez, Alberto; Zelaya Huerta, María Victoria; Cabello, Carolina; Méndez López, Iván; Mendióroz Iriarte, Maite; Ciencias de la Salud; Osasun Zientziak; Sociología y Trabajo Social; Soziologia eta Gizarte Lana; Gobierno de Navarra / Nafarroako GobernuaThe discovery of new biomarkers would be very valuable to improve the detection of early Alzheimer's disease (AD). DNA methylation marks may serve as epigenetic biomarkers of early AD. Here we identified epigenetic marks that are present in the human hippocampus from the earliest stages of AD. A previous methylome dataset of the human AD hippocampus was used to select a set of eight differentially methylated positions (DMPs) since early AD stages. Next, bisulphite pyrosequencing was performed in an expanded homogeneous cohort of 18 pure controls and 35 hippocampal samples with neuropathological changes of pure AD. Correlation between DNA methylation levels in DMPs and phospho-tau protein burden assessed by immunohistochemistry in the hippocampus was also determined. We found four DMPs showing higher levels of DNA methylation at early AD stages compared to controls, involving ELOVL2, GIT1/TP53I13 and the histone gene locus at chromosome 6. DNA methylation levels assessed by bisulphite pyrosequencing correlated with phospho-tau protein burden for ELOVL2 and HIST1H3E/HIST1H3 F genes. In this discovery study, a set of four epigenetic marks of early AD stages have been identified in the human hippocampus. It would be worth studying in-depth the specific pathways related to these epigenetic marks. These early alterations in DNA methylation in the AD hippocampus could be regarded as candidate biomarkers to be explored in future translational studies.